title: Antidepressant-like effect of α-tocopherol in a mouse model of depressive-like behavior induced by TNF-α.
abstract: Taking into account that pro-inflammatory cytokines and oxidative and nitrosative stress are implicated in the pathogenesis of depression and that α-tocopherol has antidepressant, anti-inflammatory and antioxidant properties, this study investigated the ability of α-tocopherol to abolish the depressive-like behavior induced by i.c.v. administration of TNF-α in the mouse TST. Additionally, we investigated the occurrence of changes in the levels of Bcl2 and Bax and phosphorylation of GSK-3β (Ser9) in the hippocampus of mice. The administration of TNF-α (0.001fg/site, i.c.v.) increased the immobility time in the TST, which was prevented by the administration of α-tocopherol at the doses of 10, 30 and 100mg/kg (p.o.). Subeffective doses of α-tocopherol (10mg/kg, p.o.) and/or the antidepressants fluoxetine (5mg/kg, p.o.), imipramine (0.1mg/kg, p.o.) and bupropion (1mg/kg, p.o.), the NMDA receptor antagonist MK-801 (0.001mg/kg, p.o.) or the neuronal nitric oxide synthase inhibitor 7-nitroindazole (25mg/kg, i.p.) prevented the depressive-like effect induced by TNF-α. None of the treatments altered the locomotor activity of mice. Treatment with TNF-α and/or α-tocopherol did not alter the levels of Bax and Bcl2 or the phosphorylation of GSK-3β in the hippocampus of mice. Together, our results show a synergistic antidepressant-like effect of α-tocopherol with antidepressants against the depressive-like behavior induced by an inflammatory insult, suggesting that this vitamin may be useful to optimize conventional pharmacotherapy of depression, including depressive states associated with inflammatory conditions.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Luana M
authors.initials: LM
authors.lastname: Manosso
authors.forename: Vivian B
authors.initials: VB
authors.lastname: Neis
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Daufenbach
authors.forename: Andiara E
authors.initials: AE
authors.lastname: Freitas
authors.forename: André R
authors.initials: AR
authors.lastname: Colla
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D024502:alpha-Tocopherol / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D014409:Tumor Necrosis Factor-alpha; D024502:alpha-Tocopherol
keywords: Antidepressant; CNS; FST; GSK-3; IFN; IL; Inflammation; N-methyl-d-aspartate; NMDA; NO; O.D.; TNF-α; TST; Tail suspension test; central nervous system; forced swimming test; glycogen synthase kinase-3; i.c.v.; i.p.; interferon; interleukin; intracerebroventricular; intraperitoneal; nNOS; neuronal nitric oxide synthase; nitric oxide; optical density; p.o.; per oral; tail suspension test; tumor necrosis factor-α; α-Tocopherol